With chemotherapy treatment, 80-90% of children with acute myeloid leukemia (AML) achieve remission. However, 30-40% of these patients subsequently suffer recurrence, and the long-term survival rate is only 50%. Novel therapies are urgently needed to prevent or treat recurring AML. Parthenolide, a naturally-occurring compound, induces robust AML cell killing and has the potential to reduce recurrence of AML by killing cells resistant to traditional chemotherapeutics and responsible for relapse.